Download PDF
Arzneimittelforschung 2008; 58(3): 136-140
DOI: 10.1055/s-0031-1296483
Antiemetics · Gastrointestinal Drugs · Urologic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Effect of the Administration of Monofluorophosphate on Alpha-Macroglobulin Levels and the Clinical Course of Pancreatitis in Rats

E Verónica
Bone Biology and Mineral Metabolism Laboratory, Rosario National University School of Medicine, Rosario, Argentina
,
Di Loreto
Bone Biology and Mineral Metabolism Laboratory, Rosario National University School of Medicine, Rosario, Argentina
,
Stella M Roma
Bone Biology and Mineral Metabolism Laboratory, Rosario National University School of Medicine, Rosario, Argentina
,
Inés Menoyo
Bone Biology and Mineral Metabolism Laboratory, Rosario National University School of Medicine, Rosario, Argentina
,
Alfredo Rigalli
Bone Biology and Mineral Metabolism Laboratory, Rosario National University School of Medicine, Rosario, Argentina
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)

    Permissions and Reprints

Abstract

Clinical course of pancreatitis depends partially on the proteinases-antiproteinases balance. Monofluorophosphate (CAS 10163-15-2, MFP) binds to plasmatic antiproteinase alpha-macroglobulin (AM), modifies its homeostasis and, as a consequence, has potential effects on the progression of pancreatitis and other inflammatory processes. The progress of incomplete closed duodenal loop induced pancreatitis was studied in rats with AM homeostasis perturbed by the oral administration of MFP. Twelve rats received 80 µmol MFP/day orally for one month before the induction of pancreatitis. Controls did not receive MFP. Plasmatic amylase activity and AM levels were measured. The day of death was recorded and histopathology of pancreas was performed. Higher survival and less histopathologic changes were observed in rats treated with MFP previous to pancreatitis compared to rats without MFP. Amylase activities were higher in controls and AM levels decreased significantly in controls respect to MFP-treated animals.

Higher survival, lower amylasemia and less pancreatic damage in MFP-treated animals suggest a protective effect of the drug in the clinical course of pancreatitis.

Key words

CAS 10163-15-2 - Macroglobulin - Monofluorophosphate, anti-pancreatitic activity, effect on alpha-macroglobulin levels - Pancreatitis
 

  • Literature

  • 1 Saluja AK, Steer MLP. Patophysiology of pancreatitis. Role of cytokines and other mediators of inflammation. Digestion. 1999; 60 (1) 27-33
    CrossrefPubMedGoogle Scholar
  • 2 Frossard JL, Hadengue A, Pastor CM. New serum markers for the detection of severe acute pancreatitis in humans. Am J Respir Crit Care Med. 2001; 164: 162-170
    CrossrefPubMedGoogle Scholar
  • 3 Norton ID, Cain JE. Optimising outcomes in acute pancreatitis. Drugs. 2001; 61 (11) 1581-1591
    CrossrefPubMedGoogle Scholar
  • 4 Seta T, Noguchi Y, Shimada T, Shi Kata S, Fukui T. Treatment of acute pancreatitis with protease inhibitors: a meta-analysis. Eur J Gastroenterol Hepatol. 2004; 16 (12) 1287-1293
    CrossrefPubMedGoogle Scholar
  • 5 Cavalini G, Frulloni L. Antiproteasic agents in the prevention of post-ERCP pancreatitis: rationale for use and clinical results. JOP, J Pancreas. 2003; 4 (1) 75-82
    PubMedGoogle Scholar
  • 6 Borth W. α2-Macroglobulin, a multifunctional binding protein with targeting characteristics. FABEB J. 1992; 6: 3345-3353
    PubMedGoogle Scholar
  • 7 Sottrup-Jensen L. α-macroglobulins: structure, shape and mechanism of proteinase complex formation. J Biol Chem. 1989; 264: 11539-11542
    PubMedGoogle Scholar
  • 8 Umans L, Seneels L, Overbergh L, Stas L, Van Leuven F. Alpha 2-macroglobulin and murino globulin-1 deficienct mice. A mouse model for acute pancreatitis. Am J Pathol. 1999; 155 (3) 983-993
    CrossrefPubMedGoogle Scholar
  • 9 Lasson A, Laurell AB, Ohlsson K. Correlation among complement activation, protease inhibitors, and clinical course in acute pancreatitis in man. Scand J Gastroenterol. 1985; 20 (3) 335-345
    CrossrefPubMedGoogle Scholar
  • 10 Sebert JL, Richard P, Mennecier I, Bisset JP, Loeb G. Monofluorophosphate increase lumbar bone density in osteopenic patients: A double-masked ramdomized study. Osteoporosis Int. 1995; 5: 108-114
    CrossrefPubMedGoogle Scholar
  • 11 Delmas PD, Dupuis J, Duboeuf F, Chapuy MC. Meunier PI. Treatment of vertebral osteoporosis with disodium monofluorophosphate: comparison with sodium fluoride. J Bone Mineral Res. 1990; 5: S143-S147
    PubMedGoogle Scholar
  • 12 Rigalli A, Esteban L, Pera L, Puche RC. Binding of monofluorophosphate to α-2-macroglobulin and C3. Calcif Tissue Int. 1997; 60 (1) 86-89
    CrossrefPubMedGoogle Scholar
  • 13 Pera L, Rigalli A, Morosano M, Masoni A, Bocanera R, Tozzini R. Niveles plasmáticos de α2-macroglobulina (α2M) y C3 en el tratamiento crónico con MFP. Rev Argentina Endocrinol Metab. 1996; 33: 244-
    PubMedGoogle Scholar
  • 14 Esteban L, Rigalli A, Puche RC. Metabolism of the complex monofluorophosphate-α-2-macroglobulin in the rat. Medicina (B Aires). 1999; 59: 151-156
    PubMedGoogle Scholar
  • 15 Calderari S, Font MT, Garroq O, Martínez SM, Puche RC, Tarrés MC. The inbred IIM/Fm stock. Rat Newsletter. 1991; 25: 28-29
    PubMedGoogle Scholar
  • 16 Guide for the care and use of laboratory animals. Publication N° 86-23, revised. National Institutes of Health; Bethesda, MD (USA): 1985
    Google Scholar
  • 17 Sugimoto M, Takada T, Yasuda H. A new experimental pancreatitis by incomplete closed duodenal loop. Pancreas. 2004; 28: 112-119
    CrossrefPubMedGoogle Scholar
  • 18 Hoffmann EM, Muetzel S, Becker K. A modified dot-blot method of protein determination applied in the tannin-protein precipitation assay to facilitate the evaluation of tannin activity in animal feeds. Br J Nutr. 2002; 87: 421-426
    CrossrefPubMedGoogle Scholar
  • 19 Graph Pad Prism [computer program]. Version 2.0. San Diego, CA (USA): GraphPad Software; 1994
    Google Scholar
  • 20 Hoogerwerf WA. Pharmacological management of pancreatitis. Curr Opin Pharmacol. 2005; 5: 578-582
    CrossrefPubMedGoogle Scholar
  • 21 Rigalli A, Ballina JC, Beinlich A, Alloatti R, Puche RC. Pharmacokinetics differences between sodium fluoride and sodium monofluorphosphate and comparative bone mass increasing activity of both compounds, in the rat. Arzneimittel-Forschung (Drug Research). 1994; 44: 762-766
    PubMedGoogle Scholar
  • 22 Hegyi P, Rakonczay Z, Sári R, Lonovics J, Takács T, Czakó L. L-arginine-induced experimental pancreatitis. World J Gastroenterol. 2004; 10: 2003-2009
    PubMedGoogle Scholar
  • 23 Weidenbach H, Lerch MM, Schoenberg MH, Gress TM, Turi S, Adler G. Characterization of a non-invasive, vascular model of acute necrotizing pancreatitis. J Gastroenterol. 1996; 34: 9-14
    PubMedGoogle Scholar